tbuckley/cabot-search huggingface dataset:
A Third-Generation Bisphosphonate, Minodronic Acid (YM529), Augments the Interferon α/β-Mediated Inhibition of Renal Cell Cancer Cell Growth Both <i>In vitro</i> and <i>In vivo</i>
Authors: Takeshi Yuasa, Masaki Nogawa, Shinya Kimura, Asumi Yokota, Kiyoshi Sato, Hidekazu Segawa, Junya Kuroda, Taira Maekawa
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Minodronic acid (YM529) is a third-generation nitrogen-containing bisphosphonate. Here, we have investigated the therapeutic efficacy of YM529 against renal cell cancer (RCC) alone or in combination with IFN both in vitro and in vivo. Experimental Design: One murine and eight human RCC cell lines were used for the in vitro studies and were subjected to a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting. Luciferase-labeled murine RCC cells (RENCALuc) were transplanted into the s.c. tissue or the renal subcapsule of syngeneic BALB/c mice. These mice were treated with YM529 and/or murine IFN and the growth of the cancer cells was monitored by an in vivo imaging system. Results: YM529 inhibited the growth of RCC cells in a dose- and time-dependent manner and enhanced the growth inhibitory potential of IFN in vitro. In the in vivo mouse models, YM529 did not markedly inhibit the RCC cell growth on its own but it augmented the anticancer effect of IFN (P &amp;lt; 0.05). The YM529-treated mice (with or without IFN) did not alter the γ/δ T-lymphocyte numbers. The various treatment regimens were also not associated with any adverse effects. However, YM529 combined with IFN reduced the serum vascular endothelial growth factor levels. Conclusions: Our study suggests that YM529 may be a potent anticancer agent for RCC. The efficacy and safety of IFN plus YM529 as a therapy for RCC should be verified by early-phase clinical trials.
The Aging of America
Authors: Edward L. Schneider
Journal: JAMA (1990)

The rapid growth of the oldest age groups will have a major impact on future health care costs. We use current US Census Bureau projections for the growth of our oldest age groups to project future costs for Medicare, nursing homes, dementia, and hip fractures. Without major changes in the health of our older population, these health care costs will escalate enormously, in large part as a result of the projected growth of the "oldest old," those aged 85 years and above. Medicare costs for the oldest old may increase sixfold by the year 2040 (in constant 1987 dollars). It is unlikely that these projected increases in health care costs will be restrained solely by cost-containment strategies. Successful containment of these health care costs will be related to our ability to prevent and/or cure those age-dependent diseases and disorders that will produce the greatest needs for long-term care. (<i>JAMA</i>. 1990;263:2335-2340)
Selective Anterior Hypophysectomy in the Treatment of Diabetic Retinopathy
Authors: Jules Hardy
Journal: JAMA (1968)

On the basis of Houssay's phenomenon and of Poulsen's report of a patient who had a selective necrosis of the anterior lobe of the hypophysis with a permanent cure of the diabetic retinopathy, it would seem that the most physiologic approach to the treatment of progressive diabetic retinopathy would be a selective and complete anterior hypophysectomy. In order to accomplish this, a microsurgical technique for dissection of the hypophysis through a transsphenoidal midline approach was developed and used in 17 consecutive cases. A selective anterior hypophysectomy was achieved in 11 patients. The other six patients had a total hypophysectomy. Significant reduction in the insulin requirements occurred in all of the patients. Diabetes insipidus occurred in six patients. Within the follow-up period of a few months to two years, it appeared that diabetic retinopathy might have been favorably influenced in 15 patients.
Identification of the Critical Oxygen Delivery for Anaerobic Metabolism in Critically III Septic and Nonseptic Humans
Authors: Juan J. Ronco
Journal: JAMA (1993)

<h3>Objectives.</h3> —To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. <h3>Design.</h3> —Cohort analytic study, consecutive sample. <h3>Setting.</h3> —Two tertiary care medical and surgical intensive care units in university hospitals. <h3>Patients.</h3> —Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. <h3>Methods and Interventions.</h3> —The O<sub>2</sub>consumption (determined by indirect calorimetry), O<sub>2</sub>delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5-to 20-minute intervals while life support was discontinued. <h3>Main Outcome Measures.</h3> —Critical O<sub>2</sub>delivery, critical O<sub>2</sub>extraction ratio, and maximal O<sub>2</sub>extraction ratio. <h3>Results.</h3> —In all septic and eight nonseptic patients, O<sub>2</sub>delivery and O<sub>2</sub>consumption displayed a biphasic relationship over the range of O<sub>2</sub>delivery studied. There were no differences in critical O<sub>2</sub>delivery threshold (3.8±1.5 vs 4.5±1.3 mL·min<sup>-1</sup>·kg<sup>-1</sup>;<i>P</i>&gt;.28), critical O<sub>2</sub>extraction ratio (0.61 ±0.05 vs 0.59±0.16;<i>P</i>&gt;.64), and maximal O<sub>2</sub>extraction ratio (0.74±0.08 vs 0.80±0.11;<i>P</i>&gt;.29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL·min<sup>-1</sup>·kg<sup>-1</sup>in the critical O<sub>2</sub>delivery and 0.1 in the critical and maximal O<sub>2</sub>extraction ratios between the septic and nonseptic groups. <h3>Conclusions.</h3> —The critical O<sub>2</sub>delivery for anaerobic metabolism was identified from the biphasic relationship between O<sub>2</sub>delivery and O<sub>2</sub>consumption in individual humans. The critical O<sub>2</sub>delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O<sub>2</sub>delivery for anaerobic metabolism or tissue O<sub>2</sub>extraction ability. Interventions to increase O<sub>2</sub>delivery to supranormal levels in critically ill humans in the hope of increasing O<sub>2</sub>consumption may be inappropriate. (<i>JAMA</i>. 1993;270:1724-1730)
Multivitamin/Folic Acid Supplementation in Early Pregnancy Reduces the Prevalence of Neural Tube Defects
Authors: Aubrey Milunsky
Journal: JAMA (1989)

We examined the relation of multivitamin intake in general, and folic acid in particular, to the risk of neural tube defects in a cohort of 23 491 women undergoing maternal serum α-fetoprotein screening or amniocentesis around 16 weeks of gestation. Complete questionnaires and subsequent pregnancy outcome information was obtained in 22 776 pregnancies, 49 of which ended in a neural tube defect. The prevalence of neural tube defect was 3.5 per 1000 among women who never used multivitamins before or after conception or who used multivitamins before conception only. The prevalence of neural tube defects for women who used folic acid-containing multivitamins during the first 6 weeks of pregnancy was substantially lower—0.9 per 1000 (prevalence ratio, 0.27; 95% confidence interval, 0.12 to 0.59 compared with never users). For women who used multivitamins without folic acid during the first 6 weeks of pregnancy and women who used multivitamins containing folic acid beginning after 7 or more weeks of pregnancy, the prevalences were similar to that of the nonusers and the prevalence ratios were close to 1.0. (<i>JAMA</i>. 1989;262:2847-2852)
Screening for Gestational Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2014)

Description: Update of the 2008 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for gestational diabetes mellitus (GDM). Methods: The USPSTF reviewed the evidence on the accuracy of screening tests for GDM, the benefits and harms of screening before and after 24 weeks of gestation, and the benefits and harms of treatment in the mother and infant. Population: This recommendation applies to pregnant women who have not been previously diagnosed with type 1 or 2 diabetes mellitus. Recommendation: The USPSTF recommends screening for GDM in asymptomatic pregnant women after 24 weeks of gestation. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for GDM in asymptomatic pregnant women before 24 weeks of gestation. (I statement)
Association of Blue Light–Filtering Intraocular Lenses With All-Cause and Traffic Accident–Related Injuries Among Patients Undergoing Bilateral Cataract Surgery in Finland
Authors: Piotr Kanclerz, Idan Hecht, Mariana Cunha, Boris Knyazer, Ilkka Laine, Raimo Tuuminen
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Blue light–filtering (BLF) intraocular lenses (IOLs) have been widely used in clinical practice for more than 20 years and have been implanted in millions of patients with cataracts worldwide. However, little evidence on the association of BLF IOLs with injuries is available. <h3>Objective</h3> To assess the association of BLF IOLs with all-cause and traffic accident–related injuries and quality of vision while driving after bilateral cataract surgery. <h3>Design, Setting, and Participants</h3> This retrospective registry-based cohort study included patients who underwent bilateral cataract surgery between September 3, 2007, and December 14, 2018, and were followed until December 14, 2021. Surgery was performed at the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. The 4986 participants received non-BLF IOLs (n = 2609) or BLF IOLs (n = 2377) in both eyes. Patients undergoing bilateral surgery between 2015 to 2016 with non-BLF IOLs (n = 102) or BLF IOLs (n = 91) and currently driving a car were interviewed using a structured questionnaire for visual performance while driving. <h3>Exposures</h3> Follow-up for a mean (SD) of 2166 (1110) days after second eye surgery. <h3>Main Outcomes and Measures</h3> Kaplan-Meier and multivariable Cox proportional hazards regression analyses for the risk of all-cause and traffic accident–related injuries after surgery in the second eye obtained from the patient medical records were assessed. To improve follow-up precision, both death and the end of the follow-up were used as censoring events. <h3>Results</h3> A total of 4986 patients were included in the analysis (1707 [34.2%] men and 3279 [65.8%] women; mean [SD] age, 73.2 [8.6] years at the first surgery and 74.3 [8.8] years at the second). Injury-free survival rates preceding the first eye surgery were comparable between the non-BLF and BLF IOL groups (hazard ratio adjusted for age and sex, 0.95 [95% CI, 0.81-1.13;<i>P</i> = .57]). In multivariable Cox proportional hazards regression analysis controlling for age and sex, the use of BLF IOLs showed no advantage in overall injuries compared with the use of non-BLF IOLs (hazard ratio, 0.99 [95% CI, 0.88-1.11];<i>P</i> = .85) or in any injury subtype. Subjective visual performance parameters for driving were all comparable between the non-BLF and BLF IOL groups except for glare when driving in the dark (evening or night), which occurred among 9 of 80 patients with BLF IOLs compared with 0 of 83 non-BLF IOLs (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that use of BLF IOLs was not associated with reduced risk of injuries, whereas glare during nighttime driving was significantly worse in the BLF IOL group with pseudophakia.
Nonselective beta blockers, hepatic decompensation, and mortality in cirrhosis: A national cohort study
Authors: Marina Serper, David E. Kaplan, Tamar H. Taddei, Elliot B. Tapper, Jordana B. Cohen, Nadim Mahmud
Journal: Hepatology (2022)

Little is known about the effectiveness of nonselective beta blockers (NSBBs) in preventing hepatic decompensation in routine clinical settings. We investigated whether NSBBs are associated with hepatic decompensation or liver-related mortality in a national cohort of veterans with Child-Turcotte-Pugh (CTP) A cirrhosis with no prior decompensations.
Evaluation of Functional Recovery Following Thrombectomy in Patients With Large Vessel Occlusion and Prestroke Disability
Authors: Maximilian I. Sprügel, Jochen A. Sembill, Svenja Kremer, Stefan T. Gerner, Michael Knott, Stefan Hock, Tobias Engelhorn, Arnd Dörfler, Hagen B. Huttner, Stefan Schwab
Journal: JAMA Network Open (2022)

<h3>Importance</h3> It is uncertain whether thrombectomy is associated with benefits in patients with prestroke disability. <h3>Objective</h3> To evaluate the use of thrombectomy for patients with large vessel occlusion and prestroke disability. <h3>Design, Setting, and Participants</h3> This cohort study included patients with large vessel occlusion stroke and prestroke disability (modified Rankin Scale score, 3 or 4) admitted to a single tertiary care center between January 1, 2006, and June 30, 2019 (controls: 2006-2015; thrombectomy: 2015-2019). Follow-up was conducted at 90 days. Data analysis was performed from November 1 to December 31, 2021. <h3>Exposures</h3> Use of thrombectomy vs no thrombectomy. <h3>Main Outcomes and Measures</h3> The primary outcome was functional recovery at 90 days defined as clinical recovery to the functional status before stroke onset. Secondary outcomes included functional dependency, mortality, early neurologic improvement, and recanalization. <h3>Results</h3> Among 205 patients (149 women [72.7%]; median age, 82 years [IQR, 75-87 years]), 102 individuals (49.8%) received thrombectomy and 103 (50.2%) were controls. Thrombectomy was significantly associated with functional recovery (thrombectomy, 20 [19.6%]; controls, 8 [7.8%]; adjusted difference, 9.4%; 95% CI, 2.2% to 16.7%;<i>P</i> = .005). Secondary outcomes showed differences in mortality, early neurologic improvement, and recanalization in favor of thrombectomy treatment. The rate of functional dependency did not differ significantly between the 2 groups (adjusted difference, 8.9%; 95% CI, −2.5% to 20.2%;<i>P</i> = .13). The rate of functional recovery after thrombectomy was 44.0% for patients with early neurologic improvement, 29.4% for patients with small infarct volume (&lt;50 mL), and 7.0% for patients with neither of these parameters. <h3>Conclusions and Relevance</h3> Findings of this study suggest that selected patients with prestroke disability may benefit from thrombectomy. However, the thrombectomy-associated increase in functional recovery was small. Therefore, routine use of thrombectomy may not be beneficial among patients with a large ischemic core and infarct volumes less than 50 mL may be necessary to obtain functional recovery. Patients with higher chances of functional recovery are also at an increased risk of survival with substantial disability, indicating potential harms from the intervention; further studies are needed.
Midwifery in General Practice
Journal: BMJ (1926)

SIR,-I understand tlhere is sholrtly to be in force a Regulation wlhich lays down that every practitioner attend- ing a midwifery case must notify such case to the medical officer of health if the temperature should be 100.40 for twenty-foul hours; that he is to state what vaginal exam- inationis he lhas made, also vaginal examinationls miiade by otlhels un-der himi, andl the niames and addresscs of suchl pers11)ns; anid that he is to supply a kind of r6s&umdi of the health of the patient before and after confinlement.I amii i21 a country practice, and my confinements amiiouiut to eighity or ninety a yealr, for which I receive £1 1Cs.eachi (wheni paid).There is no district nurse in the village andl no qualified midwife.The people are poor wolrking-class, anid would be deeply insulted were I to demand a fee for ante-inatal examination.After this Regulationi comes into force my only course, as far as I can see, will be to drop midwifery work unless I cani obtain the assistance of a qualified midwife.Midwifery practice is slowly but surely slipping into the hands of certificated mi1idwives.The majority of the doctors in this district, as in many others, have given up attending conifinements amiiong their poorer patients.This is partly, no doubt, because of the small fees, but largely, I believe, oni accounit of the red tape now prevalent, and because the blame for whatever goes wrong is laid at the practitioner's door.
CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling
Authors: Tao Xie, Du-jiang Fu, Zhi-min Li, Dao-jun Lv, Xian-Lu Song, Yu-zhong Yu, Chong Wang, Kang-jin Li, Baoqian Zhai, Jiacheng Wu, Ning-Han Feng, Shan-Chao Zhao
Journal: Molecular Cancer (2022)

Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain.Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1.CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression.CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.
Effect of a Multicomponent Intervention on Hepatic Steatosis Is Partially Mediated by the Reduction of Intermuscular Abdominal Adipose Tissue in Children With Overweight or Obesity: The EFIGRO Project
Authors: Cristina Cadenas-Sanchez, Fernando Idoate, Rafael Cabeza, Arantxa Villanueva, Beatriz Rodríguez-Vigil, María Medrano, Maddi Osés, Francisco B. Ortega, Jonatan R. Ruiz, Idoia Labayen
Journal: Diabetes Care (2022)

In adults, there is evidence that improvement of metabolic-associated fatty liver disease (MAFLD) depends on the reduction of myosteatosis. In children, in whom the prevalence of MAFLD is alarming, this muscle-liver crosstalk has not been tested. Therefore, we aimed to explore whether the effects of a multicomponent intervention on hepatic fat is mediated by changes in intermuscular abdominal adipose tissue (IMAAT) in children with overweight/obesity.A total of 116 children with overweight/obesity were allocated to a 22-week family-based lifestyle and psychoeducational intervention (control group, n = 57) or the same intervention plus supervised exercise (exercise group, n = 59). Hepatic fat percentage and IMAAT were acquired by MRI at baseline and at the end of the intervention.Changes in IMAAT explained 20.7% of the improvements in hepatic steatosis (P < 0.05). Only children who meaningfully reduced their IMAAT (i.e., responders) had improved hepatic steatosis at the end of the intervention (within-group analysis: responders -20% [P = 0.005] vs. nonresponders -1.5% [P = 0.803]). Between-group analysis showed greater reductions in favor of IMAAT responders compared with nonresponders (18.3% vs. 0.6%, P = 0.018), regardless of overall abdominal fat loss.The reduction of IMAAT plays a relevant role in the improvement of hepatic steatosis after a multicomponent intervention in children with overweight/obesity. Indeed, only children who achieved a meaningful reduction in IMAAT at the end of the intervention had a reduced percentage of hepatic fat independent of abdominal fat loss. Our findings suggest that abdominal muscle fat infiltration could be a therapeutic target for the treatment of MAFLD in childhood.
A unique immune signature in blood separates therapy-refractory from therapy-responsive acute graft-versus-host disease
Authors: Astrid G. S. van Halteren, Jessica S. Suwandi, Sander Tuit, Jelske Borst, Sandra Laban, Roula Tsonaka, Ada Struijk, Anna-Sophia Wiekmeijer, Melissa van Pel, Bart O. Roep, Jaap Jan Zwaginga, Arjan C. Lankester, Koen Schepers, Maarten J. D. van Tol, Willem E. Fibbe
Journal: Blood (2022)

Acute graft-versus-host disease (aGVHD) is an immune cell‒driven, potentially lethal complication of allogeneic hematopoietic stem cell transplantation affecting diverse organs, including the skin, liver, and gastrointestinal (GI) tract. We applied mass cytometry (CyTOF) to dissect circulating myeloid and lymphoid cells in children with severe (grade III-IV) aGVHD treated with immune suppressive drugs alone (first-line therapy) or in combination with mesenchymal stromal cells (MSCs; second-line therapy). These results were compared with CyTOF data generated in children who underwent transplantation with no aGVHD or age-matched healthy control participants. Onset of aGVHD was associated with the appearance of CD11b+CD163+ myeloid cells in the blood and accumulation in the skin and GI tract. Distinct T-cell populations, including TCRγδ+ cells, expressing activation markers and chemokine receptors guiding homing to the skin and GI tract were found in the same blood samples. CXCR3+ T cells released inflammation-promoting factors after overnight stimulation. These results indicate that lymphoid and myeloid compartments are triggered at aGVHD onset. Immunoglobulin M (IgM) presumably class switched, plasmablasts, and 2 distinct CD11b- dendritic cell subsets were other prominent immune populations found early during the course of aGVHD in patients refractory to both first- and second-line (MSC-based) therapy. In these nonresponding patients, effector and regulatory T cells with skin- or gut-homing receptors also remained proportionally high over time, whereas their frequencies declined in therapy responders. Our results underscore the additive value of high-dimensional immune cell profiling for clinical response evaluation, which may assist timely decision-making in the management of severe aGVHD.